Natural polyisoprene rubber, which is obtained from Hevena brasiliensis rubber trees, has been used extensively as a material of construction for elastomeric dip-molded medical devices and medical device components. Examples of these devices and components are surgical gloves, examination gloves, finger cots, catheter balloons, uterine thermal ablation balloons, catheter cuffs, condoms, contraceptive diaphragms, in-dwelling urinary drainage catheters, and male external urinary drainage catheters.
Dip-molding of natural rubber is performed with either a latex (an aqueous dispersion of rubber particles) or an organic solution of the rubber. Dipping in either the latex or the organic solution is followed by removal of the water or solvent, and the dipping and water or solvent removal are often performed in repeated cycles to achieve a particular film thickness. The film thus formed is then vulcanized to bring the rubber to a fully cured state. In some procedures, prevulcanization is practiced, i.e., vulcanization of the rubber in the dipping medium prior to the dipping step. A film from a prevulcanized dipping medium does not require curing after the dipping step, but instead only drying to remove the water. In further procedures, both prevulcanization and post-curing, i.e., vulcanization both of the dipping solution prior to dipping and of the film after dipping, are used.
In latex dipping, the thickness of the final article is often increased by the use of a coagulant, either as a preliminary coagulant dip or a heat-sensitized coagulant dip. Solvent dipping (the use of an organic solution of the rubber rather than a latex) is performed with any of various solvents, such as benzene, toluene, gasoline, aliphatic hydrocarbons, cycloaliphatic hydrocarbons such as cyclopentane and cyclohexane, and solvent combinations such as hexane and acetone.
Whether a latex or an organic solution is used, articles and devices formed from natural rubber are responsible for a variety of health problems. Some users experience allergic reactions which either begin within minutes of exposure or hours later. Symptoms range from mild reactions such as skin redness, hives or itching, to more serious reactions such as runny nose, itchy eyes, scratchy throat, difficulty in breathing, coughing spells, and wheezing, and in extreme cases, life-threatening shock. When strong reactions are experienced, they are similar in nature to those resulting from bee stings.
Adverse reactions to natural rubber are generally of three types. The first is an irritant dermatitis, which involves skin irritation that is not related to the body's immune response. Although not an allergic reaction, irritant dermatitis can cause breaks in the skin which can provide the components of the rubber, including proteins present in the rubber, with increased access to the body's immune system and lead to a latex allergy. The second type is a delayed cutaneous hypersensitivity, also known as a Type IV allergy. Type IV allergies are generally caused by chemicals such as thiurams that are incorporated into the rubber for vulcanization purposes. This type of reaction is mediated via T-cells, generally occurs within 6 to 48 hours of contact with the rubber article, and is localized to the area of the skin where contact has been made. The third type of reaction is termed an "immediate reaction" and also known as a Type I allergy. Type I allergies are systemic allergic reactions caused by IgE antibodies to the proteins in the natural rubber. Symptoms include hives, rhinitis, conjunctivitis, asthma, and in rare cases anaphylaxis and hypotension. Type I reaction symptoms generally occur within about 30 minutes of exposure.
Thus, the adverse reactions caused by natural rubber are due either to chemicals added to the rubber to promote vulcanization, particularly sulfur-containing chemicals, or to the proteins that remain in the rubber when the rubber is extracted from its natural source. To address the protein-derived reactions, methods of treating natural rubber have been developed to reduce its protein content. One method of achieving this is by a double centrifuge method of processing natural rubber latex--a first centrifuge step removes some of the aqueous phase, and is followed by the addition of water and a second centrifuge step to remove the added water and the protein. This removes some of the protein but not all. Another method has involved the use of enzymes to digest the proteins. This again removes only some of the proteins, not all, and leaves enzymes which are themselves proteins in the latex.
In any event, de-proteinized natural rubber fails to offer the level of performance that is achieved with natural rubber that has not been de-proteinized. Comparative test results are reported by Nakade, S., et al., "Highly Purified Natural Rubber IV. Preparation and Characteristics of Gloves and Condoms," J. Nat. Rubb. Res. 12(1): 33-42 (1997). These results show that de-proteinized natural rubber has tensile modulus values and a tear strength level that are lower than those of natural rubber. These deficiencies relative to natural rubber remain even through the use of vulcanization of the rubber by irradiation. A study reported by Mohid, N., et al., "Characterization of NR Latex and Vulcanization," Nippon Genshiryoku Kenkyusho, 1990: JAERI-M-89-228, Proc. Int. Symp. Radiat. Vulcanization Nat. Rubber Latex, Tokyo/Takasaki, July 1989, pages 157-163, shows that the tensile properties of irradiated de-proteinized rubber are inferior to those of irradiated natural rubber.
Various synthetic elastomers have been used as substitutes for natural rubber. Nitrile and chloroprene synthetic rubber materials, for example, have been used in the manufacture of surgical gloves, medical examination gloves, and dental gloves. These materials do not however match the high resiliency and low tensile set values of natural rubber. Silicone rubber has been used for catheter balloons, but its tensile strength is low relative to natural rubber and must be compensated for by an increased thickness. Polyurethane has also been used as a natural rubber substitute, particularly in dip-molded catheter balloons. Polyurethanes have very high tensile strength but lack the resiliency and low tensile set values of natural rubber. As a result, polyurethanes are not suitable for devices that are required to undergo large degrees of expansion during use and to return to their original configuration upon depressurization. Also, because of their thermoplastic nature, polyurethanes tend to soften and are prone to leakage at elevated temperatures which diminishes their usefulness for devices such as uterine thermal ablation balloons. Gloves have also been prepared from styrene-ethylenelbutylene-styrene tri-block copolymer, but this material suffers from low tensile set values and poor dimensional stability when heated.
The use of formulations based on or derived from cis-1,4-polyisoprene for dip-molded products has been disclosed. One such disclosure is that of Hirai et al., U.S. Pat, No. 3,971,746, issued Jul. 27, 1976. Hirai et al. disclose the use of a cis-1,4-polyisoprene that has been modified by the introduction of carbonyl groups into the polymer structure, after having recognized that products formed from the unmodified polymer are deformed upon removal from the mold and contains streaks and grooves that render them mechanically deficient. Preiss et al., U.S. Pat. No. 3,215,649, disclose the use of a sulfur-vulcanized cis-1,4-polyisoprene.
To summarize the collective teachings of the prior art, cis-1,4-polyisoprene without the protein that is retained from natural rubber sources is believed to be unsuitable for dip-molded medical devices since products made from deproteinized natural rubber lack the tensile characteristics that are important features of these devices, even those products made from deproteinized rubber that has been crosslinked by irradiation. This expectation is reinforced by molecular weight considerations, the isoprene in natural rubber has a high molecular weight component of from about 1,000,000 amu to about 2,500,000 amu (number average), while synthetic polyisoprene has a considerably lower molecular weight with a number average ranging from about 250,000 amu to about 350,000 amu. A lower molecular weight polymer is expected to have lesser tensile properties, including tensile set values. Synthetic polyisoprene also has a lower degree of branching, lower symmetry, and lower intermolecular forces. All of these characteristics contribute to and affect the tensile properties of the polymer. Furthermore, the prior art distinctly avoids mention of any crosslinking method other than the use of sulfur-containing compounds. Thus, there is no disclosure in the prior art of a dip-molded product of synthetic cis-1,.sup.4 -polyisoprene that is both protein-free and sulfur-free and that has tensile characteristics that are acceptable for medical devices, particularly those that undergo an elastic expansion during use on the order of 100% (i.e., twice its unexpanded size) or greater.